This invention relates to novel 1,2- and 1,3-(di-O-n-alkyl) glycerol derivatives, which are useful as non-specific stimulants of cell-mediated immunity in warm-blooded animals. In particular, these novel compounds and related compounds have been found to be useful in the stimulation of antitumoral activity, especially when used in conjunction with conventional cytoreductive therapy. These compounds are also useful as vaccine adjuvants, i.e., are useful in conjunction with known immunological substances in order to induce or enhance the immunogenic response of the latter.
It is known that biological vaccines such as Corynebacterium parvum and BCG, a viable strain of Mycobacterium bovis, and the synthetic levamisole have utility as immune stimulants of the reticulo-endothelial system and are capable of increasing the resistance of a warm-blooded animal to tumors. However, the use of these agents has been restricted by hepatic-renal toxicity, granuloma formation, neutropenia and inconsistent therapeutic effects. Accordingly, it has been of continuing interest to develop non-biological, systemically active immune stimulants. It has further been of interest to develop compounds which are useful as vaccine adjuvants, in order to induce or enhance the effects of conventional vaccines. For discussions of the stimulation of cell-mediated immunity and antitumoral activity, see Herberman, Adv. Cancer Res., 19, 207 (1971), Jordan and Merigan, Ann. Rev. Pharmacol., 15, 157 (1975), Levy and Wheelock, Adv. Cancer Res., 20, 131 (1972) and Sinkovics, Post Graduate Medicine, 59, 110 (1976).
U.S. Pat. No. 2,738,351 discloses the compounds of the general formula ##STR1## wherein each of R.sub.1 and R.sub.2 may be alkyl, unsubstituted or substituted aryl or aralkyl, each of X, Y and Z may be oxygen, sulfur or sulfonyl, ALK is straight or branched alkylene of from 1 to 6 carbon atoms, and B may be di(lower)-alkylamino, piperidino, morpholino, pyrrolidino, lower alkyl-pyrrolidino, N'-alkylpiperazino or pipecolino, as local anesthetic agents. Additionally, the discussion of alternate synthetic routes in said patent discloses intermediates of the above formula wherein B is amino and lower alkyl amino. However, none of the compounds specifically enumerated in the disclosure of said patent contains an alkyl R.sub.1 or R.sub.2 larger than n-pentyl. Further, in none of these compounds are both R.sub.1 and R.sub.2 alkyl and both X and Y oxygen.
Insecticidal and miticidal compounds of the formula ##STR2## wherein R.sub.1 and R.sub.2 may each be, inter alia, lower alkylthio; q is 0 to 5 and A may be, inter alia, 1-piperidino or di-lower alkyl amino are disclosed in Japanese Pat. No. J7-6042-177.
Applicant's copending U.S. patent application Ser. No. 825,535 filed Aug. 18, 1977 discloses, inter alia, compounds of the formulae ##STR3## wherein R is hydrogen or alkyl of 1 to 6 carbon atoms and R.sub.1 and R.sub.2 are each n-alkyl of 12 to 20 carbon atoms. These compounds are disclosed to be useful as antiviral agents.